New research shows that schizophrenia is not a single disease, but a group of eight distinct disorders, each caused by changes in clusters of genes that lead to different sets of symptoms.

The finding sets the stage for scientists to develop better ways to diagnose and treat schizophrenia, a mental illness that can be devastating when not adequately managed, says C. Robert Cloninger, co-author of the study published Monday in the American Journal of Psychiatry.

“We are really opening a new era of psychiatric diagnosis,” says Cloninger, professor of psychiatry and genetics at the Washington University School of Medicine in St. Louis. Cloninger says he hopes his work will “allow for the development of a personalized diagnosis, opening the door to treating the cause, rather than just the symptoms, of schizophrenia.”

Clonginger and colleagues found that certain genetic profiles matched particular symptoms. While people with one genetic cluster have odd and disorganized speech – what is sometimes called “word salad” – people with another genetic profile hear voices, according to the study, funded by the National Institutes of Health.

Dr. C. Robert Cloninger, Washington University School of Medicine, and colleagues found that certain genetic profiles matched particular symptoms of schizophrenia.(Photo: Robert Boston, Washington University)

Some genetic clusters gave people higher risks of the disease than others, according to the study, which compared the DNA of 4,200 people with schizophrenia to that of 3,800 healthy people.

One set of genetic changes, for example, confers a 95% chance of developing schizophrenia. In the new study, researchers describe a woman with this genetic profile who developed signs of the disorder by age 5, when she taped over the mouths of her dolls to make them stop whispering to her and calling her name. Another patient – whose genetic profile gave her a 71% risk of schizophrenia – experienced a more typical disease course and began hearing voices at age 17.

The average person has less than a 1% risk of developing schizophrenia, Cloninger says.

“It underlines that the way we diagnose schizophrenia is relatively primitive,” Marder says.

Patients may wait years for an accurate diagnosis, and even longer to find treatments that help them without causing intolerable side effects.

Doctors have long known that schizophrenia can run in families, says Robert Freedman, editor in chief of the American Journal of Psychiatry and chair of psychiatry at the University of Colorado Anschutz Medical Campus. If one identical twin has schizophrenia, for example, there is an 80% chance that the other twin has the disease, as well.

In the past, doctors looked for single genes that might cause schizophrenia, without real success, Freedman says.

The new paper suggests that genes work together like a winning or losing combination of cards in poker, Freedman says. “This shows us that there are some very bad hands out there,” Freedman says.

Doctors have known for years that breast cancer is not one disease, but at least half a dozen diseases driven by different genes, says study co-author Igor Zwir, research associate in psychiatry at Washington University.(Photo: Robert Boston, Washington University)

In some cases – in which a genetic profile conveys close to a 100% risk of schizophrenia – people may not be able to escape the disease, Cloninger says. But if doctors could predict who is at high risk, they might also be able to tailor an early intervention to help a patient better manage their condition, such as by managing stress.

Doctors don’t yet know why one person with a 70% risk of schizophrenia develops the disease and others don’t, Clonginger says. It’s possible that environment plays a key role, so that child with a supportive family and good nutrition might escape the diagnosis, while someone who experiences great trauma or deprivation might become very ill.

The study also reflects how much has changed in the way that scientists think about the genetic causes of common diseases, Marder says. He notes that diseases caused by a single gene – such as sickle-cell anemia and cystic fibrosis – affect very few people. Most common diseases, such as cancer, are caused by combinations of genes. Even something as apparently simple as height is caused by combinations of genes, he says.

Doctors have known for years that breast cancer is not one disease, for example, but at least half a dozen diseases driven by different genes, says study co-author Igor Zwir, research associate in psychiatry at Washington University. Doctors today have tests to predict a woman’s risk of some types of breast cancer, and other tests that help them select the most effective drugs.

Those sorts of tests could be extremely helpful for people with schizophrenia, who often try two or three drugs before finding one that’s effective, Cloninger says.

“Most treatment today is trial and error,” Cloninger says.

If doctors could pinpoint which drugs could be the most effective, they might be able to use lower doses, producing fewer of the bothersome side effects that lead many patients to stop taking their medication, Cloninger says.